US3096337A - Process for the preparation of amino-halogenopyridines - Google Patents
Process for the preparation of amino-halogenopyridines Download PDFInfo
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- US3096337A US3096337A US5661A US566160A US3096337A US 3096337 A US3096337 A US 3096337A US 5661 A US5661 A US 5661A US 566160 A US566160 A US 566160A US 3096337 A US3096337 A US 3096337A
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- 238000000034 method Methods 0.000 title claims description 28
- 238000002360 preparation method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000007858 starting material Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- UVNWMIHXIIMNHU-UHFFFAOYSA-N pent-2-enedinitrile Chemical compound N#CCC=CC#N UVNWMIHXIIMNHU-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- -1 amino- Chemical class 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 description 3
- 239000012433 hydrogen halide Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UVNWMIHXIIMNHU-OWOJBTEDSA-N (e)-pent-2-enedinitrile Chemical class N#CC\C=C\C#N UVNWMIHXIIMNHU-OWOJBTEDSA-N 0.000 description 2
- BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 2
- QUXLCYFNVNNRBE-UHFFFAOYSA-N 6-methylpyridin-2-amine Chemical compound CC1=CC=CC(N)=N1 QUXLCYFNVNNRBE-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical class ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- SLMHHOVQRSSRCV-UHFFFAOYSA-N 2,3-dibromopyridine Chemical compound BrC1=CC=CN=C1Br SLMHHOVQRSSRCV-UHFFFAOYSA-N 0.000 description 1
- FEYDZHNIIMENOB-UHFFFAOYSA-N 2,6-dibromopyridine Chemical compound BrC1=CC=CC(Br)=N1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 description 1
- DDCDTWPTVDVDDU-UHFFFAOYSA-N 2-hydroxypentanedinitrile Chemical class N#CC(O)CCC#N DDCDTWPTVDVDDU-UHFFFAOYSA-N 0.000 description 1
- JFRMZVKWPONIDN-UHFFFAOYSA-N 4-bromo-3-hydroxybutanenitrile Chemical compound BrCC(O)CC#N JFRMZVKWPONIDN-UHFFFAOYSA-N 0.000 description 1
- LHBPNZDUNCZWFL-UHFFFAOYSA-N 4-chloro-3-hydroxybutanenitrile Chemical compound ClCC(O)CC#N LHBPNZDUNCZWFL-UHFFFAOYSA-N 0.000 description 1
- ABYCTYJDRLQBMT-UHFFFAOYSA-N 6-bromo-4-methylpyridin-2-amine Chemical compound CC1=CC(N)=NC(Br)=C1 ABYCTYJDRLQBMT-UHFFFAOYSA-N 0.000 description 1
- YGGUZZJLGAUOLQ-UHFFFAOYSA-N 6-iodopyridin-2-amine Chemical compound NC1=CC=CC(I)=N1 YGGUZZJLGAUOLQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
Definitions
- 2-amino-6-bromopyridine and related compounds have been prepared previously by the action of ammonia on 2,6-dibromopyridine.
- This material in accordance with existing practice is prepared by the bromination of pyridine at 500 C., but the process is unwieldy to thepoint that yields at' best are a marginal 17%.
- the compounds can be-made bybromination of pyridines at about 300 C. in the presence of r'ouprous ibromide with yields of the dibromopyridine in such case being as high as 66%.
- the process isconcerned with a method of preparing amino-'halogenopyridine compounds from 'epichlorohydrin compounds and cyanides wherein the process involves, first, forming a 1,3-dicyanopropanol-2 compound from the starting material selected from the group consisting of an epichlorohydrin; a LS-dichloropropanol-Z; a 3-hydroxy-4- chlorobutyronitrile; an epibromohydrin; a 1,3-di-bromopropanol-Z; or a 3-hydroxy-4-bromobutyronitrile; any glutacononitrile derivative from the 1,3-dicyanopropanol compounds by dehydration may he used or glutacononitriles Where the double bond is part of aromatic ring system, any 1,3-dicyanopropene derivable from 1,3-dicyanopropanol-Z compounds by dehydration may be used: any 1,3-d
- R R R represents any organic or inorganic radical and X represents the halogen. If it is desired to produce a compound with other than a halogen on the ring, an acid other'than a halogen acid is used in the reaction.
- the solvent In the reaction forming the amino-halogenopyridine, if it is desired to use a solvent the solvent must be one which does not participate in the reaction or react with the hydrogen halide used in the process.
- the starting materials which include any compound having the basic structure, defined more generally, may
- R and R positions will carry-in the R and R positions cyanide groups and inthe R R and R positions will carry any organic or inorganic radical except that combination wherein R and R are cyanide radicals.
- R and R and .R R may-be anyjpartof an aromatic ring system.
- raw materials. for the reaction maybe such organic compound and any acid HX, wherein X is a halogen.
- 1,3-dicyanopropanol-2 1,3-dicyano-2- methylpropanol-Z, 1,3-dicyanopropene, 1,3-dicyano-2 phenylpropanol-Z, 1,3-dicyano-2 ethylpropanol-Zahd compounds of the formulas and N bN
- the preferred range of temperature is from about --35 to 250 C., whereas the ratio of hydrogen halide to organic starting material should be at least 1:1.
- R radicals correspond to the R radicals delined in connection with the specification of starting material.
- the starting material is selected to orient a substituent R R or R in a desired position, because the dicyano-3 carbon nucleus moiety used for the formation of a material is traceable in the product of reaction by noting that the heterocyclic nitrogen atom in the pyridine ring is one of the nitrogens of the starting material and the nitrogen atom in the amino group is the other nitrogen atom of the starting dicyano compound.
- Example I Preparation of 2-Amin0-6-Br0mopyridine 1,3-dicyanopropanol-2 (1 pant) was added to a mixture of ether parts) and methylene chloride (20 parts). Hydrogen bromide gas (anhydrous) was passed through the solution and a solid material quickly precipitated. Magnetic Stirring was maintained during the introduction of the gas. When the solvent was saturated with hydrogen bromide, the flask was stoppered and the mixture allowed to stand overnight. The contents of the flask were poured into sodium hydrogen carbonate solution (saturated; about 100 parts) and methylene chloride (30 parts) added. The .organic layer was separated, washed with water and dried.
- Hydrogen bromide gas anhydrous
- the present invention differs trom the known art in being an entirely new method whereby one can synthesize a pyridine derivative. It also has the advantage over the known art that Z-amino-halogenopyridines previously available by multi-step procedure, can now be prepared efliciently by a one-step method starting with 1,3-dicyanopropanol-2 and its analo'gs.
- Example IIl The Preparation of 2-Amz'no-4-Methylfi-Bromopyridine 1,3-dicyano-2-methylpropanol-2 (1 part) was added to other (5 parts). Anhydrous hydrogen bromide was bubbled through the biphasic liquid and after ten minutes the solution became homogeneous. Passage of the gas was continued for an additional half hour. The contents of the flask were then poured into a saturated solution of sodium hydrogen carbonate (50 parts). The white crystalline precipitate of 2-amino-4-methyl-6-bromopyridine (1.32 parts) was removed by filtration and air-dried, M.P.
- R is a member selected from the group consisting of hydrogen, lower alkyl and phenyl and X is a halo .gen atom' selected from the group consisting of bromine and iodine, which process comprises reacting in an inert organic solvent at room temperature a compound selected from the group consisting of R. NCOH2(:]CHg-CN 7 OH where R has the same meaning as above and the correspending unsaturated compound formed upon splitting out of water with an anhydrous hydrogen halide of the formula HX Where X has the same meaning as above and recovering said first-named compound.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Description
3,096,337 PROCESS FOR THEPREPARATION F AMINO-HALQGENOPYREDINES Francis Johnson, West Newton, Mass., assignor to The Dow Chemical Company, Midlanil, Mich., a corporationof Delaware No Drawing. Filed Feb. 1, 1960, Ser. No. 5,661 '6 Claims. (Q1. 260-296) invention relatesto new'pyridine compounds and to a method of preparing such amin'o-halogenopyridine compounds by means of a convenient synthetic path, commencing with a carbon compound, such, e.g., as a 1,3, dicyanopropanol-Z and substituted variants of such compounds.
2-amino-6-bromopyridine and related compounds have been prepared previously by the action of ammonia on 2,6-dibromopyridine. This material in accordance with existing practice is prepared by the bromination of pyridine at 500 C., but the process is unwieldy to thepoint that yields at' best are a marginal 17%. Also the compounds can be-made bybromination of pyridines at about 300 C. in the presence of r'ouprous ibromide with yields of the dibromopyridine in such case being as high as 66%.
Other amino halogenopyridines are prepared in accordance with similar synthetic routes. Another recently recorded method independent of the one described in this application as a subject of this invention has 'to do with the use of 2-amino-6-methylpyridine for the synthesis of 2-amino-6-halogenopyridine compounds. These methods have in common the disadvantage of .relying upon rare starting materials or on long awkward synthetic paths. :Where the synthesis route is long, the loss incurred at one point in the route is expanded to a considerable loss of yield by virtue of the fact that low fractional yields in a series of steps causes the yield to approach zero as a limit.
Accordingly, it is an object of this invention to provide a method of synthesizing amino-halogenoapyridine derivatives.
It is also another object of the invention to provide a method of preparing 1,3-dicyanopropanol-2 and similar compounds as precursor materials especially useful in the synthesis of the amino-halogeno-pyridine compounds.
Other objects and advantages of the invention will in part be obvious and in part appear hereinafter.
In accordance with this invention, therefore, the process isconcerned with a method of preparing amino-'halogenopyridine compounds from 'epichlorohydrin compounds and cyanides wherein the process involves, first, forming a 1,3-dicyanopropanol-2 compound from the starting material selected from the group consisting of an epichlorohydrin; a LS-dichloropropanol-Z; a 3-hydroxy-4- chlorobutyronitrile; an epibromohydrin; a 1,3-di-bromopropanol-Z; or a 3-hydroxy-4-bromobutyronitrile; any glutacononitrile derivative from the 1,3-dicyanopropanol compounds by dehydration may he used or glutacononitriles Where the double bond is part of aromatic ring system, any 1,3-dicyanopropene derivable from 1,3-dicyanopropanol-Z compounds by dehydration may be used: any 1,3-dicyanopropene wherein the double bond is part of an aromatic ring system may be used such as Thereafter reacting the 1,3-dicyanopropanol-2 or 1,3-dicyanopropene or glutacononitrile formed or an appropriice 2 ately substituted version thereof, with an anhydrous halogen acid, either with or without the presence of a solvent, thereby produces the amino-'halogenopyridine corresponding to the following:
NJ-NH:
wherein R R R represents any organic or inorganic radical and X represents the halogen. If it is desired to produce a compound with other than a halogen on the ring, an acid other'than a halogen acid is used in the reaction.
In the reaction forming the amino-halogenopyridine, if it is desired to use a solvent the solvent must be one which does not participate in the reaction or react with the hydrogen halide used in the process.
The starting materials which include any compound having the basic structure, defined more generally, may
be any compound containing the following internal structural moiety:
wherein X=halogen, or cyano group, which, when appropriately substituted and/or converted as follows:
will carry-in the R and R positions cyanide groups and inthe R R and R positions will carry any organic or inorganic radical except that combination wherein R and R are cyanide radicals. R and R and .R R may-be anyjpartof an aromatic ring system. Thus raw materials. for the reaction maybe such organic compound and any acid HX, wherein X is a halogen. As :specific examples of the starting organic compound there may be mentioned 1,3-dicyanopropanol-2, 1,3-dicyano-2- methylpropanol-Z, 1,3-dicyanopropene, 1,3-dicyano-2 phenylpropanol-Z, 1,3-dicyano-2 ethylpropanol-Zahd compounds of the formulas and N bN
In general in carrying out the process the preferred range of temperature is from about --35 to 250 C., whereas the ratio of hydrogen halide to organic starting material should be at least 1:1.
Accordingly, it will be seen that the process is readily adaptable to the preparation of such compounds as substituted aminobromoalkylpyridines such e.g., as 2-amino- 6-bromo-4-ethyl pyridine and others. In general those compounds which can be made according to the process may be represented by the following drawing:
a NiN'Hz and where R and- R and R and R can be part of an aromatic ring system.
wherein the R radicals correspond to the R radicals delined in connection with the specification of starting material.
It will be seen from the general drawing of the final product of reaction that the starting material is selected to orient a substituent R R or R in a desired position, because the dicyano-3 carbon nucleus moiety used for the formation of a material is traceable in the product of reaction by noting that the heterocyclic nitrogen atom in the pyridine ring is one of the nitrogens of the starting material and the nitrogen atom in the amino group is the other nitrogen atom of the starting dicyano compound.
Reference to the following specific examples will more clearly illustrate the fundamental reaction involved in the formation of the compounds:
Example I.Preparation of 2-Amin0-6-Br0mopyridine 1,3-dicyanopropanol-2 (1 pant) was added to a mixture of ether parts) and methylene chloride (20 parts). Hydrogen bromide gas (anhydrous) was passed through the solution and a solid material quickly precipitated. Magnetic Stirring was maintained during the introduction of the gas. When the solvent was saturated with hydrogen bromide, the flask was stoppered and the mixture allowed to stand overnight. The contents of the flask were poured into sodium hydrogen carbonate solution (saturated; about 100 parts) and methylene chloride (30 parts) added. The .organic layer was separated, washed with water and dried. Removal of the solvent gave a pale brown crystalline solid which was recrystallized from methylene chloride-petrol ether (charcoal decolorization). This yielded 2 amino-6-bromopyridine (1 part) M.P. 89-90". Analysis.Calcd. for C H N Br: C, 34.68; H, 2.89; Br, 46.24; N, 16.2. Found: C, 34.8; H, 3.0; Br, 46.1; N, 16.1%. Other 2-amino-6-halogenopyridines are prepared similarly. Another recently reported method, unrelated to the one described in this patent application, relies on the use of 2-amino-6-methyl pyridine for the synthesis of 2-amino-6-halogenopyridine materials. These methods suffer from the disadvantages of limited availability of starting materials, or long un- Wieldy synthetic paths. The present invention differs trom the known art in being an entirely new method whereby one can synthesize a pyridine derivative. It also has the advantage over the known art that Z-amino-halogenopyridines previously available by multi-step procedure, can now be prepared efliciently by a one-step method starting with 1,3-dicyanopropanol-2 and its analo'gs.
- Example ll.--The Preparation of 2-Amz'n0-6- Iodopyridine 1,3-dicyanopropanol-2 (1 part) was added to anhydrous ether (30 par-ts). Dry hydrogen iodide was then bubbled through the biphasic liquid for 1 hour until the ethereal solution was saturated. The flask was then stoppered and allowed to stand overnight. The reaction mixture was then poured into sodium hydrogen carbonate solution (saturated; parts) containing a little sodium thiosulfate. This aqueous material was then extracted with methylene chloride and the organic layer separated and dried. Removal of the methylene chloride gave a mass of dark crystals. Crystallization (charcoal decolorization) of this material from acetone yielded a crop of light tan-colored crystals (1.4 parts). Further recrystallization of this material from ether-petrol ether, gave the analytically pure 2-amino-6-iodopyridine, M.P. 109110. Analysis.--Oalcd. for C H N I: C, 27.30; H, 2.30; N, 12.74; I, 57.69. Found: C, 27.30; H, 2.40; N, 12.60; I, 57.50%.
Example IIl.-The Preparation of 2-Amz'no-4-Methylfi-Bromopyridine 1,3-dicyano-2-methylpropanol-2 (1 part) was added to other (5 parts). Anhydrous hydrogen bromide was bubbled through the biphasic liquid and after ten minutes the solution became homogeneous. Passage of the gas was continued for an additional half hour. The contents of the flask were then poured into a saturated solution of sodium hydrogen carbonate (50 parts). The white crystalline precipitate of 2-amino-4-methyl-6-bromopyridine (1.32 parts) was removed by filtration and air-dried, M.P. Further recrystallization of this product from water or from ether-petrol ether, did not efiect any improvement in the melting point. Analysis.-Calcd. for C H N Bi-z C, 38.53; H, 3.77; N, 14.96. Found: C, 38.4; H, 3.8; N, 14.9.
What is claimed is: 1. A process for the preparation of a compound of the formula X N NH:
wherein R is a member selected from the group consisting of hydrogen, lower alkyl and phenyl and X is a halo .gen atom' selected from the group consisting of bromine and iodine, which process comprises reacting in an inert organic solvent at room temperature a compound selected from the group consisting of R. NCOH2(:]CHg-CN 7 OH where R has the same meaning as above and the correspending unsaturated compound formed upon splitting out of water with an anhydrous hydrogen halide of the formula HX Where X has the same meaning as above and recovering said first-named compound.
2. The method in accordance with claim 1 in which the starting material is 1,3-dicyanopropanol-2.
3. The method in accordance with claim 1 in which the starting material is 1,3-dicyano-2-rnethylpropanol-2.
4. The method in accordance with claim 1. in which the starting material is NCCH CH=CHCN 5. The method in accordance with claim 1 in which the starting material is 6 6. The method in accordance with claim 1 in which the starting material is OHqOH GHr- -GHa N OH N References Cited in the file of this patent Sell et al.: J. Chem. Soc., vol. 73, pp. 777-780 (1898).
Sell et al.: J. Chem. Soc., vol. 77, pp. 771-774 (1900).
Sell et al.: J. Chem. Soc., vol. 77, pp. 233-235 (1900).
Lochte et al.: J. Am. Chem. Soc., "vol. 76, pp. 5548-5551 (1954),
Ma-ier-Bode: Pyridine and its Deriv., p. 143 (1934).
Klingsberg: Pyridine and its Deriv., (Part I), pp. 292-299, 342-3 (1960).
Claims (1)
1. A PROCESS FOR THE PREPARATION OF A COMPOUND OF THE FORMULA
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|---|---|---|---|
| US5661A US3096337A (en) | 1960-02-01 | 1960-02-01 | Process for the preparation of amino-halogenopyridines |
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| US5661A US3096337A (en) | 1960-02-01 | 1960-02-01 | Process for the preparation of amino-halogenopyridines |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3225041A (en) * | 1962-12-12 | 1965-12-21 | Dow Chemical Co | Process for producing 2,6-diamino pyridines |
| US3277096A (en) * | 1963-05-03 | 1966-10-04 | Dow Chemical Co | Process for the preparation of aminohalogeno isoquinolines |
-
1960
- 1960-02-01 US US5661A patent/US3096337A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3225041A (en) * | 1962-12-12 | 1965-12-21 | Dow Chemical Co | Process for producing 2,6-diamino pyridines |
| US3277096A (en) * | 1963-05-03 | 1966-10-04 | Dow Chemical Co | Process for the preparation of aminohalogeno isoquinolines |
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